Introduction Cationic domino reactions Anionic domino reactions Radical domino reactions Pericyclic domino reactions Photochemically induced domino processes Transition metal catalysis Domino reactions initiated by oxidation or reduction Enzymes in domino reactions Multicomponent reactions Special techniques in domino reactions

Domino Reactions in Organic Synthesis

The Walden memorial at the Technical University in Riga is pictured in the frontispiece to mark the recent centennial of the Walden inversion. This is a rare public monument to key events from the first era of exploration in stereocontrolled synthesis, and may be the only such monument to use the language of organic chemistry expressed at the molecular level. The reaction of racemic substrates with chiral nucleophiles is one of many methods currently known to achieve kinetic resolution, a phenomenon that ranks as the oldest and most general approach for the synthesis of highly enantioenriched substances. The first nonenzymatic kinetic resolutions as well as the original forms of the Walden inversion were studied in the 1890s. All of these investigations were conducted within the first generation following the demonstration that carbon is tetrahedral, and provided abundant evidence that the principles and importance of enantiocontrolled syntheses were understood. However, a reliable, rapid technique to quantify results and guide the optimization process was still lacking. Many decades passed before this problem was solved by the advent of HPLC and GLPC assays on chiral supports, which stimulated explosive growth in the synthesis of nonracemic substances by kinetic resolution. The Walden monument is accessible to passers-by for hands-on inspection as well as for contemplation and learning. In a similar way, kinetic resolution is experimentally accessible and can be thought-provoking at several levels. We follow the story of kinetic resolution from the early discoveries through fascinating historical milestones and conceptual developments, and close with a focus on modern techniques that maximize efficiency.

Efficiency in nonenzymatic kinetic resolution.

Synthesis of secondary amines

Die organisch-chemische Synthese hat stets eine grose Faszination auf den Chemiker ausgeubt, und sie wird auch in Zukunft nichts von ihrer Bedeutung verlieren. Es ist eine Binsenweisheit, das alle Chemiker - und nicht nur die - auf die Synthese chemischer Verbindungen, mit denen sie arbeiten wollen, angewiesen sind. So ist die organisch-chemische Synthese heute mehr denn je die Schnittstelle von Organischer Chemie, Biologie. Biochemie, Medizin, Physik und Materialwissenschaft. Man sollte auch nicht vergessen, das die Grundlage der chemischen Industrie die Synthese ist. Fur den Synthetiker aus Leidenschaft aber ist die Synthese weit mehr als nur Mittel zu dem Zweck, Verbindungen in die Hand zu bekommen; sie ist Ausdruck seiner Kreativitat. Intelligenz und seines handwerklichen Konnens, aber auch seiner Ausdauer.

Sequentielle Transformationen in der Organischen Chemie eine Synthesestrategie mit Zukunft

Enantioselective enzymatic desymmetrizations in organic synthesis.

The bridged, pentacyclic intermediate 2 for atisine (1) was synthesized in a naturally occurring enantiomeric form from dimethyl cyclohexanone-2,6-dicarboxylate (6). The synthesis is composed of the following key steps: (1) formation of the azabicyclo [3.3.1] nonane by a double Mannich reaction, (2) enantioselective conversion by a lipase-catalyzed acylation, (3) stereoselective hydroboration in the presence of BF 3 .Et 2 O, and (4) construction of the bicyclo [2.2.2] octane ring system by an intramolecular double Michael reaction

Asymmetric total synthesis of atisine via intramolecular double Michael reaction

Stereoselective total synthesis of (.+-.)-atisine via intramolecular double Michael reaction

Three 1-phenyl-1,2,3,4-tetrahydroisoquinoline alkaloids, cryptostylines I, II, and III, have been synthesized in racemic forms via a aryl radical-initiated cyclization.

Synthesis of racemic cryptostylines I, II, and III by radical cyclization.

Aryl radical-initiated cyclization of the ketimines derived from acetophenone and benzophenone occurred exclusively at the nitrogen end of the azomethine bond in an exo-5 mode to yield the corresponding indoline derivatives

Indoline formation by regioselective aryl radical cyclization to azomethine bond

Treatment of racemic 2-trimethylsilylethynyl-2-cyclopentenol [(±)- 1 ] with vinyl acetate in the presence of lipase PS in toluene yielded a 1:1 mixture of the unreacted ( S )-alcohol [( S )- 1 ] and the ( R )-acetate [( R )- 7 which without isolation afforded the chirally homogeneous ( R )-alcohol [( R )- 1 ] in 73% overall yield on reaction with acetic acid in the same reaction medium in the presence of diisopropyl azodicarboxylate and triphenylphosphine, followed by reductive deacylation of the resulting ( R )-acetate [( R )- 7 ]. On the other hand, hydrolysis of the racemic acetate [(±)- 7 ], obtained from [(±)- 1 ], in a phosphate buffer solution in the presence of lipase PS yielded a 1:1 mixture of the ( R )-alcohol [( R )- 1 ] and the unreacted ( S )-acetate [( S )- 7 ] which without separation, furnished the enantiomerically homogeneous ( S )-alcohol [( S )- 1 ] in 75% overall yield on treatment with acetic acid under the above Mitsunobu conditions, followed by reductive deacylation of the resulting ( S )-acetate [( S )- 7 ].

Enantiocomplementary preparation of optically pure 2-trimethylsilylethynyl-2-cyclopentenol by homochiralization of racemic precursors: a new route to the key intermediate of 1,25-dihydroxycholecalciferol and vincamine

M. Suzuki

Papers

Asymmetric total synthesis of atisine via intramolecular double Michael reaction

Stereoselective total synthesis of (.+-.)-atisine via intramolecular double Michael reaction

Synthesis of racemic cryptostylines I, II, and III by radical cyclization.

Indoline formation by regioselective aryl radical cyclization to azomethine bond

Enantiocomplementary preparation of optically pure 2-trimethylsilylethynyl-2-cyclopentenol by homochiralization of racemic precursors: a new route to the key intermediate of 1,25-dihydroxycholecalciferol and vincamine